Helicobacter (H.) pylori infections in humans are a major cause of gastric and duodenal ulceration as well as gastric cancer. Triple therapies with proton pump inhibitors and clarithromycin and amoxicillin are recommended as first line treatment. These standard therapies increasingly face problems with antibiotic resistance and recurrence of infection, especially in areas where H. pylori is endemic. Various studies in animal models have shown the feasibility of both prophylactic and therapeutic vaccination against H. pylori (Del Guidice (2001) Annu. Rev. Immunol. 19, 523-563; Sanchez et al. (2001) FEMS Immunol Med. Microbiol. 30, 157-165). H. pylori proteins expressed in infected mice and hence exposed to the mouse immune system, appear similar to those detected in human infections, suggesting that the mouse model is suitable for the preclinical screening of antigen candidates (Bumann et al. (2002) Inf. Imm. 70, 6494-6498). Immunizations with recombinant urease was found to induce local and serum immune responses in mice and protect against Helicobacter pylori infection (Kleanthous et al. (1998) Inf. Imm. 66, 2879-2886).
H. pylori is not the only bacterial pathogen capable of colonizing the human gastric mucosa. “H. heilmannii” indeed has been found in approximately 0.96% of gastric biopsies. This organism is strongly associated with gastritis, but also with peptic ulceration, gastric adenocarcinoma and mucosa associated lymphoid tissue (MALT) lymphoma.
Some studies revealed sufficient antigenic cross-reactivity between H. felis and H. pylori to generate protection to H. felis challenge following immunization with a H. pylori sonicated antigen solution (Lee & Chen (1994) Inf. Imm. 62, 3594-3597; Michettti et al. (1994) Gastroenterology 107, 1002-1011). One study shows that H. heilmannii infection can be prevented by vaccination both with H. heilmannii UreB and H. pylori UreAB, confirming that protective immunity against Helicobacter infections can be elicited by homologous as well as heterologous Helicobacter urease (Dieterich et al. (1999) Inf. Imm. 67, 6206-6209).
Recently it has been shown that H. heilmannii does not represent a single species, but a group of different bacterial species with a similar spiral morphology, most of which are probably zoonotic in origin. On the basis of 16S rRNA sequences, “H. heilmannii” has been classified into two types (Solnick et al. (1993) J. Infect. Dis. 168, 379-385). ‘H. heilmannii’type 2 organisms are closely related, if not identical, to the canine and feline Helicobacter spp., namely H. felis, H. bizzozeronii and H. salomonis. More than 50% of the “H. heilmannii” infections in humans however are due to “H. heilmannii” type I. It is now accepted that “H. heilmannii” type 1 is identical to “Candidatus H. suis” (O'Rourke et al. (2004) Int J Syst Evol Microbiol. 54, 2203-2212; De Groote et al. (1999) Int. J. Syst. Bacteriol. 49, 1769-1777), a spirally shaped bacterium that colonizes the stomach of more than 60% of slaughterpigs.
Little information is available in the literature on the potential of vaccine-induced protection against non-pylori helicobacter strains, such as “Candidatus H. suis”. In vitro cultivation of “Candidatus H. suis” currently is not possible, but mouse inoculation can be used to grow and maintain this bacterium viable for more than two years starting from infected pig stomach mucosa (Mendes et al., (1991) cited above; Dick et al. (1989) J. Med. Microbiol. 29, 55-62; Park et al., (2003) J. Comp. Pathol. 129:154-160).